Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates
<p>Abstract</p> <p>Background</p> <p>Aggregation of soluble, monomeric β- amyloid (Aβ) to oligomeric and then insoluble fibrillar Aβ is a key pathogenic feature in development of Alzheimer’s disease (AD). Increasing evidence suggests that toxicity is linked to diffusibl...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-12-01
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| Series: | Journal of Biomedical Science |
| Subjects: | |
| Online Access: | http://www.jbiomedsci.com/content/19/1/104 |
| _version_ | 1828474368474218496 |
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| author | Sharoar Md Thapa Arjun Shahnawaz Mohammad Ramasamy Vijay Woo Eun-Rhan Shin Song Park Il-Seon |
| author_facet | Sharoar Md Thapa Arjun Shahnawaz Mohammad Ramasamy Vijay Woo Eun-Rhan Shin Song Park Il-Seon |
| author_sort | Sharoar Md |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Aggregation of soluble, monomeric β- amyloid (Aβ) to oligomeric and then insoluble fibrillar Aβ is a key pathogenic feature in development of Alzheimer’s disease (AD). Increasing evidence suggests that toxicity is linked to diffusible Aβ oligomers, rather than to insoluble fibrils. The use of naturally occurring small molecules for inhibition of Aβ aggregation has recently attracted significant interest for development of effective therapeutic strategies against the disease. A natural polyphenolic flavone, Kaempferol-3-O-rhamnoside (K-3-rh), was utilized to investigate its effects on aggregation and cytotoxic effects of Aβ42 peptide. Several biochemical techniques were used to determine the conformational changes and cytotoxic effect of the peptide in the presence and absence of K-3-rh.</p> <p>Results</p> <p>K-3-rh showed a dose-dependent effect against Aβ42 mediated cytotoxicity. Anti-amyloidogenic properties of K-3-rh were found to be efficient in inhibiting fibrilogenesis and secondary structural transformation of the peptide. The consequence of these inhibitions was the accumulation of oligomeric structural species. The accumulated aggregates were smaller, soluble, non-β-sheet and non-toxic aggregates, compared to preformed toxic Aβ oligomers. K-3-rh was also found to have the remodeling properties of preformed soluble oligomers and fibrils. Both of these conformers were found to remodel into non-toxic aggregates. The results showed that K-3-rh interacts with different Aβ conformers, which affects fibril formation, oligomeric maturation and fibrillar stabilization.</p> <p>Conclusion</p> <p>K-3-rh is an efficient molecule to hinder the self assembly and to abrogate the cytotoxic effects of Aβ42 peptide. Hence, K-3-rh and small molecules with similar structure might be considered for therapeutic development against AD.</p> |
| first_indexed | 2024-12-11T05:59:32Z |
| format | Article |
| id | doaj.art-290dea6a9671420cb868b1150f805e4c |
| institution | Directory Open Access Journal |
| issn | 1021-7770 1423-0127 |
| language | English |
| last_indexed | 2024-12-11T05:59:32Z |
| publishDate | 2012-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-290dea6a9671420cb868b1150f805e4c2022-12-22T01:18:33ZengBMCJournal of Biomedical Science1021-77701423-01272012-12-0119110410.1186/1423-0127-19-104Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregatesSharoar MdThapa ArjunShahnawaz MohammadRamasamy VijayWoo Eun-RhanShin SongPark Il-Seon<p>Abstract</p> <p>Background</p> <p>Aggregation of soluble, monomeric β- amyloid (Aβ) to oligomeric and then insoluble fibrillar Aβ is a key pathogenic feature in development of Alzheimer’s disease (AD). Increasing evidence suggests that toxicity is linked to diffusible Aβ oligomers, rather than to insoluble fibrils. The use of naturally occurring small molecules for inhibition of Aβ aggregation has recently attracted significant interest for development of effective therapeutic strategies against the disease. A natural polyphenolic flavone, Kaempferol-3-O-rhamnoside (K-3-rh), was utilized to investigate its effects on aggregation and cytotoxic effects of Aβ42 peptide. Several biochemical techniques were used to determine the conformational changes and cytotoxic effect of the peptide in the presence and absence of K-3-rh.</p> <p>Results</p> <p>K-3-rh showed a dose-dependent effect against Aβ42 mediated cytotoxicity. Anti-amyloidogenic properties of K-3-rh were found to be efficient in inhibiting fibrilogenesis and secondary structural transformation of the peptide. The consequence of these inhibitions was the accumulation of oligomeric structural species. The accumulated aggregates were smaller, soluble, non-β-sheet and non-toxic aggregates, compared to preformed toxic Aβ oligomers. K-3-rh was also found to have the remodeling properties of preformed soluble oligomers and fibrils. Both of these conformers were found to remodel into non-toxic aggregates. The results showed that K-3-rh interacts with different Aβ conformers, which affects fibril formation, oligomeric maturation and fibrillar stabilization.</p> <p>Conclusion</p> <p>K-3-rh is an efficient molecule to hinder the self assembly and to abrogate the cytotoxic effects of Aβ42 peptide. Hence, K-3-rh and small molecules with similar structure might be considered for therapeutic development against AD.</p>http://www.jbiomedsci.com/content/19/1/104AβKaempferol-3-O-rhamnosideOligomerAggregationCytotoxicityAlzheimer’s disease |
| spellingShingle | Sharoar Md Thapa Arjun Shahnawaz Mohammad Ramasamy Vijay Woo Eun-Rhan Shin Song Park Il-Seon Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates Journal of Biomedical Science Aβ Kaempferol-3-O-rhamnoside Oligomer Aggregation Cytotoxicity Alzheimer’s disease |
| title | Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates |
| title_full | Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates |
| title_fullStr | Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates |
| title_full_unstemmed | Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates |
| title_short | Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates |
| title_sort | keampferol 3 o rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non toxic aggregates |
| topic | Aβ Kaempferol-3-O-rhamnoside Oligomer Aggregation Cytotoxicity Alzheimer’s disease |
| url | http://www.jbiomedsci.com/content/19/1/104 |
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